Study On The Effects And Mechanisms Of Ginseng Sini Decoction On Heart Failure

Heart failure is the terminal of most cardiovascular diseases the main cause of death in cardiovascular patients.Because of high incidence and high mortality rate,heart failure has become a major public health problem threatening human health.Energy metabolism disorder and mitochondrial dysfunction are the main factors leading to heart failure.In recent years,traditional Chinese medicine compound prescription plays an important role in the clinical treatment of heart failure by improving the cardiac function and internal environment of patients as a whole and reducing the toxic and side effects of combined western medicine.Therefore,it is of great significance to explore the mechanism of heart failure and develop new drugs of traditional Chinese medicine against heart failure.Ginseng Sini decoction?GSD?,derived from Treatise on febrile Diseases,is a classical prescription of traditional Chinese medicine composed of ginseng,aconite,dried ginger and grilled licorice,which is widely used in the treatment of heart failure in modern clinic.In this paper,the pharmacodynamics of GSD was systematically reviewed,and the mitochondrial energy metabolism and apoptosis pathway were taken as the cutting point to explore the mechanism and material basis of GSD against heart failure,so as to provide a certain basis for the development and clinical application of new drugs.In this study,the extraction process was determined by prescription analysis and orthogonal experiment,and the safety of the drug was evaluated by acute toxicity test in mice.The rat model of heart failure?heart failure,HF?was established by tail injection of adriamycin,the anti-heart failure effects of GSD were evaluated by hemodynamics and cardiac function test,and the anti-HF mechanisms of GSD were studied by qPCR and so on.The mechanisms and some material basis of anti-heart failure effects of GSD were studied by establishing heart failure model in vitro with pentobarbital sodium.Results:?The extraction process of GSD was water extraction,and there was no abnormal reaction in mice with the maximum dose of 44.44 g·kg^-1?equivalent to 171 times of the clinical dosage?.?GSD(6.776,13.552 g·kg^-1)could significantly increase left ventricular diastolic pressure,end systolic pressure and shortening rate of short axis,and decrease cardiac coefficient,CK and LDH.?GSD(6.776,13.552 g·kg^-1)could significantly decrease the contents of MDA and ROS,inhibit the activities of Na⁺-K⁺-ATPase and Ca²⁺-ATPase;GSD(13.552 g·kg^-1)could significantly up-regulate the expression of PGC-1?mRNA;and GSD(6.776,13.552 g·kg^-1)significantly down-regulated the expressions of Bax and Caspase-3 mRNA.?GSD(400 mg·L^-1),ginsenoside Rb₂?1?M?,Re?1?M?,isoliquiritigenin?80?M?and glycyrrhetinic acid?40?M?could significantly increase the cell survival rate and decrease the contents of LDH and MDA.Meanwhile,they could inhibit the activity of Na⁺-K⁺-ATPase and enhance the activity of Ca²⁺-ATPase.The expression of PGC-1?was significantly up-regulated and the expressions of Bax and Caspase-3 mRNA were down-regulated.Conclusion:According to the extraction process described in the Pharmacopoeia,the extract powder of GSD not only had no toxic and side effects in safety evaluation but also had obvious anti-heart failure effect in the body.Meanwhile,GSD and its active ingredients including ginsenoside Rb₂,ginsenoside Re,isoglycyrrhizin and glycyrrhetinic acid could reduce oxidative damage;improve mitochondrial energy metabolism by regulating Na⁺-K⁺-ATPase,Ca²⁺-ATPase activity and PGC-1?mRNA expression and inhibiting apoptosis of the mitochondrial apoptotic pathway by regulating the expression of Bax and Caspase-3 mRNA,thereby exerting a protective effect on the myocardium.In summary,this experiment provided a theoretical basis for the further development of new drugs for GSD,and laid a foundation for its research on the mechanism of anti-heart failure.